Tween 80 Exposure Induces Colitis by Disrupting Intestinal Tryptophan Metabolism

Inflammatory bowel disease (IBD) is a widespread public health problem worldwide, and environmental pollutants are regarded as the cause of IBD. Tween 80 (P80) may trigger IBD; however, its underlying mechanism of action has not been fully clarified, especially with respect to diet-induced susceptibility. This study systematically investigated the effect of P80 on the IBD development in male mice on a normal diet and high-fat diet (HFD) at an acceptable daily intake level. After 6 weeks of oral exposure to P80 (0.1, 1, 6%), the high-dose group of mice exhibited a significant increase in the disease activity index, a significant body weight loss, and a severe inflammatory response, with HFD markedly augmenting these effects. Multiomics results indicated that P80 exposure disrupted intestinal tryptophan metabolism and significantly reduced indole-3-acetic acid (IAA) levels. <i>In vivo</i> intestinal inflammation was transcriptionally regulated by genes related to the AhR/NF-κB/NLRP3 signaling pathway. Supplementing with IAA can improve inflammatory effects. <i>In vitro</i> studies confirmed that P80 exposure inhibited <i>Lactobacillus</i> from producing IAA, leading to an increase in the level of intestinal inflammation. This study revealed the specific toxic mechanism of P80-induced IBD and found that dietary factors have a synergistic toxic effect, providing new insights into the health risk assessment of environmental pollutants.